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Primary Biliary Cirrhosis
Overview Primary biliary cirrhosis is an autoimmune disease characterized by the slow, continuous degeneration of the bile ducts connecting the gallbladder to the liver. During the process of digestion, the gallbladder contracts, sending the bile into the duodenum (the beginning of the small intestine) to begin breaking down the consumed foodstuffs. The bile is produced in the liver, and carries these toxins, cholesterol, and worn down blood cells to the intestines where they can be broken down along with the partially-digested food. However, in individuals with primary biliary cirrhosis, the bile ducts which carry this fluid from the liver to the gallbladder are damaged, causing the build up of toxic bile in the liver which in turn damages the liver tissue, leading to the formation of scar tissue which may further block the bile ducts. If the disease increases in severity, it may result in irreversible scarring, fibrosis, cirrhosis, and liver failure. The cause of this disease remains unknown, though it is believed to be associated with the immune system and has been observed in higher frequency among family members in which one person is affected, leading to the hypothesis that this disease has a familial link. Influence of SNPs on Phenotype Single nucleotide polymorphisms, or SNPs, are relatively common single nucleotide variations in an organism's genome sequence that causes a difference in genotype and possibly in phenotype; this causes different alleles to arise. Due to the uncertainty surrounding the cause of this disease, most information concerning genetic links to this disease remains under study. Genes that have been connected thus far include IRF5, IL12A, SPIB, 17q12-21, and MMEL1; as well as HLA, IL12A, and IL12RB2 variants. These are all considered suggestive risk loci. Related SNPs rs10488631 in IRF5: This gene typically encodes for a protein that functions in the regulation of a specific type of cell in the immune system. Mutations in this gene have been linkied to autoimmune diseases such as systemic lupus erythematosus (lupus), rheumatoid arthritis, and inflammatory bowel disease. Though it's specific association with primary biliary cirrhosis is unclear, it has been shown to promote inflammation. Professor Burke has an increased risk of 1.31x the average person of possessing a mutation at this loci. rs574808 in IL12A: This gene encodes for a protein that functions in the production of the pro-inflammatory immune responses. Mutations in this gene have been linked to celiac disease; however, it's specific association with primary biliary cirrhosis remains unclear. Professor Burke has a decreased risk of 0.66x the average person of possessing a mutation at this loci. rs3745516 in SPIB: This gene encodes for a protein that functions in the regulation of numerous immune cell types. However, it's specific association with primary biliary cirrhosis remains unclear. Professor Burke has a increased risk of 1.64x the average person of possessing a mutation at this loci. Though most SNP associations in relation to phenotype for this disease remain relatively vague, the physical characteristics of this disease are quite clear. In addition to the degradation of bile ducts and scarring of the liver, an individual with this disease may also develop patches of small red sores across their skin which causes itching, as well as dry eyes and mouth, etc. Lessons and Implications Based on the results from 23andMe, it would be advised that individuals with this disease or with high risk for this disease stop smoking and drinking to help avoid further damage to the liver. Additionally, the affected individual may elect to obtain medication to help slow the progression of this disease. Unfortunately, there is no ultimate cure for this disease at this time. References 23andMe overview of primary biliary cirrhosis Mayo Clinic definition and overview of primary biliary cirrhosis National Institute of Diabetes and Digestive and Kidney Diseases' overview of primary biliary cirrhosis Wiki: Cirrhosis Wiki: Fibrosis Wiki: SNPs Hirschfield, G. M. "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, 20 May 2009. Web. 13 Sept. 2014. Mells, George. "Genome-wide Association Study Identifies 12 New Susceptibility Loci for Primary Biliary Cirrhosis." Nature. Nature, 13 Mar. 2011. Web. 13 Sept. 2014. .